The results of a new clinical study confirmed the high accuracy of an innovative diagnostic test to identify and classify thyroid nodules. With greater sensitivity than conventional methods, the exam, developed by the São Paulo company Onkos Molecular Diagnostics, proved to be able to avoid a large number of unnecessary surgeries. The new data reinforce that, if applied on a large scale, the innovation could generate huge savings for health plans and for the public health system.
The mir-THYpe molecular exam, which was developed with support of the Small Business Innovative Research Program (PIPE), from FAPESP (São Paulo State Research Support Foundation), and has been on the market since 2018, uses biomarkers to confirm or rule out the presence of cancer in thyroid nodules that present indeterminate results.
According to Marcos Tadeu dos Santos, founder of the company, when a nodule is identified in the thyroid, the technique used today to assess whether there is cancer or not is an aspiration puncture, with the removal of material from the patient’s neck region for visual analysis.
“The vast majority of nodules are benign, but up to 30% of them are classified as ‘indeterminate’ and, in these cases, for safety reasons, the standard procedure is surgery to extract the thyroid. However, only 25% of cases are malignant and this means that 75% of surgeries in cases of indeterminate nodules are potentially unnecessary”, he explains.
According to Santos, after the removal of the thyroid gland, the patient needs to undergo hormone replacement procedures for the rest of his life. Thus, unnecessary surgeries not only have a direct economic impact, by burdening the public and private health systems, but also generate indirect costs and long-term damage to the patient’s health.
In the last study carried out, researchers from Onkos followed for two years 440 patients who underwent the new test in all regions of Brazil. “We managed to avoid 75% of the surgeries that would be performed unnecessarily. Another interesting result is that in 92% of the cases, the use of the test changed the doctors’ clinical behavior”, said Santos. The study, presented this year at the Brazilian Thyroid Meeting, was published on the platform medRxiv, yet without peer review.
The main scientific differential of the new test, according to Santos, is that it allows the identification of the main genetic signatures of tumor cells present in the thyroid. From these markers, algorithms that use artificial intelligence decipher the molecular signatures of the tumor and give the result with high precision. The test analyzes the expression of 11 microRNAs through real-time PCR, with an accuracy of 96%.
“In addition to the diagnostic markers – which are used to determine whether the nodule is benign or malignant – we added to the exam, in 2021, some other genetic markers of a prognostic nature, that is, they allow us to determine the aggressiveness of the tumor”, says Santos.
According to him, identifying the aggressiveness of the tumor is essential to determine the planning of the surgery to be performed. “Thyroid cancer is, in general, not very aggressive. In these cases, the doctor can opt for a more conservative surgery than those recommended for more aggressive malignant nodules”, he explains.
According to Santos, the company is now requesting entry of the test in the list of exams accredited by the National Health Agency (ANS) and is seeking approval by the Unified Health System (SUS), so that the exam is offered by health plans and by the public system.
Last year, Onkos went through all the phases of the procedure to incorporate the exam on the ANS list, but the innovation has not yet been incorporated. “We are making corrections and generating new evidence to make another attempt with the ANS”, says Santos (read more in https://pesquisaparainovacao.fapesp.br/1731).
The mir-THYpe has already been coded in two tables that are a prerequisite for inclusion in the coverage of health plans: the CBHPM-AMB table, which recognizes the examination with medical procedure endorsed by the Brazilian Medical Association (AMB), and the table TUSS, which codifies procedures for health plans.
“Currently, mir-THYpe is covered by Unimed VTRP [Vales do Taquari e Rio Pardo], from Rio Grande do Sul, and we are running pilot tests in a large healthcare operator, with national coverage”, says Santos.
The company is also completing the steps for the evaluation of new technologies to be incorporated by the public system, through the National Commission for the Incorporation of Technologies in the SUS (Conitec). “This process requires cost-effectiveness studies. We had a budget approved in the PIPE program for these health technology assessment studies”, says Santos.
The first cost-effectiveness studies carried out showed excellent results, he said. “The calculation involves all the costs of the molecular exam and the surgeries it could avoid. The study showed that, with the use of the exam, the health plan saves R$ 2,000 per patient, on average”, points out Santos.
For now, access to the exam is only done privately. When the result of the gland puncture is undetermined, doctors ask the patient to perform the test directly with Onkos, or through partner laboratories.
“We have a logistical capillarity that allows us to receive samples from anywhere in Brazil. Another advantage of the test compared to others on the market is that it eliminates the need for more than one puncture of the gland, which is always uncomfortable for the patient, and samples can be transported at room temperature. Therefore, sending samples is not very complex”, evaluates Santos.
Importance of PIPE
According to Santos, the PIPE program was essential for the development of the product. At phase 1, the entire diagnostic part of the exam was developed. At phase 2 prognostic markers, which determine the aggressiveness of malignant nodules, were developed. At step 3, which has just been approved, has a technical-scientific objective and a market objective.
“In the technical-scientific part, we are going to expand the test to two new indications: for pediatric patients and for another class of nodules. In addition to the nodules identified as malignant, benign and indeterminate, about 10% are classified as ‘insufficient’, when the material extracted by the puncture is insufficient to carry out the cytological test. Our molecular examination, however, makes a diagnosis based on these samples”, says Santos.
Phase 3 of the project also secured funding for hiring an access leader – a professional who will be responsible for generating cost-effectiveness data and interacting with public and private actors in order to seek incorporation of the exam.
Onkos was incubated at Supera – Technological Innovation Park in Ribeirão Preto (SP) and the test began to be developed in 2015, in partnership with Hospital de Amor (formerly known as Hospital de Câncer de Barretos). The product was launched in 2018 and, according to Santos, the platform may also be adapted in the future to other types of cancer, such as breast and prostate cancer.
The article “Real-world, prospective, and multicenter validation of a microRNA-based molecular thyroid classifier” (DOI: 10.1101/2020.10.27.20217356), by Marcos Tadeu dos Santos, Bruna Moretto Rodrigues, Satye Shizukuda, David Livingstone Alves Figueiredo, Giulianno Molina de Melo, Rubens Adão da Silva, Claudio Fainstein, Gerson Felisbino dos Reis, Rossana Corbo, Helton Estrela Ramos, Fernanda Vaisman and Mário Vaisman, can be read on the platform medRxiv in https://www.medrxiv.org/content/10.1101/2020.10.27.20217356v1.full.